Development of Drug Dual-Carriers Delivery System with Mitochondria-Targeted and PH/Heat Responsive Capacity for Synergistic Photothermal-Chemotherapy of Ovarian Cancer

Overview

Journal Int J Nanomedicine

Publisher Dove Medical Press

Specialty Biotechnology

Date 2020 Feb 6

PMID 32021181

Citations 5

Authors

Xiaoxia Guo

Jie Mei

Chunping Zhang

Affiliations

Soon will be listed here.

Abstract

Purpose: Multifunctional drug delivery systems (DDS) are emerging as a new strategy to highly treat malignant tumors. The aim of this study is to develop a drug dual-carriers delivery system (DDDS) using the natural protein ferritin (FRT) and a nanoscale graphene oxide (NGO) as dual-carriers.

Methods: The FRT is a pH-sensitive hollow cage protein with disassembly and reassembly properties and the NGO has a large surface area and a photothermal effect by which it can load and release drugs under near-infrared irradiation (NIR). Due to these unique features, the NGO loaded the anticancer drug resveratrol (RSV) and the conjugated mitochondrion targeted molecule IR780 as IR780-NGO-RSV (INR), the first drug delivery platform. Next, the INR was capsulated by FRT to form the DDDS INR@FRT which was applied for synergistic photothermal-chemotherapy of ovarian cancer.

Results: Through a series of characterizations, INR@FRT showed a uniform nanosphere structure and remarkable stability in physiological condition. Heat/pH 5.0 was confirmed to trigger RSV release from the INR@FRT. After taken up by cells, INR@FRT located to the lysosomes where the acidic environment triggered INR release. INR targeted the mitochondrion and released RSV to directly react with organelles, which in turn decreased the mitochondrion membrane potential and caused cell apoptosis. In-vivo experiments showed that INR@FRT combined with NIR irradiation displayed remarkable tumor suppression with a high survival rate after 60 days of treatment. Finally, the biocompatibility of INR@FRT was demonstrated in vitro and in vivo.

Conclusion: These results highlight the immense potential of INR@FRT as a type of DDDS for the treatment of tumors.

Citing Articles

Graphene-Based Nanomaterials for Photothermal Therapy in Cancer Treatment.

Baez D Pharmaceutics. 2023; 15(9).

PMID: 37765255 PMC: 10535159. DOI: 10.3390/pharmaceutics15092286.

Ferritin-based nanomedicine for disease treatment.

Zhu Y, Zhu Y, Cao T, Liu X, Liu X, Yan Y Med Rev (2021). 2023; 3(1):49-74.

PMID: 37724111 PMC: 10471093. DOI: 10.1515/mr-2023-0001.

Ferritin in cancer therapy: A pleiotropic tumoraffin nanocage-based transport.

Deng G, Li Y, Liang N, Hu P, Zhang Y, Qiao L Cancer Med. 2023; 12(10):11570-11588.

PMID: 36999977 PMC: 10242860. DOI: 10.1002/cam4.5778.

Alkannin Inhibits the Development of Ovarian Cancer by Affecting miR-4461.

Wang Y, Zhang J, Wang F, Chen W, Ma J, Wang H Evid Based Complement Alternat Med. 2021; 2021:5083302.

PMID: 34876915 PMC: 8645362. DOI: 10.1155/2021/5083302.

Bioengineered Ferritin Nanocarriers for Cancer Therapy.

Sun X, Hong Y, Gong Y, Zheng S, Xie D Int J Mol Sci. 2021; 22(13).

PMID: 34209892 PMC: 8268655. DOI: 10.3390/ijms22137023.

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